Anti-human tenascin monoclonal antibody
a technology of human tenascin and monoclonal antibody, which is applied in the field of antihuman tenascin monoclonal antibody, can solve the problems of limiting the use and quality of life of patients, bc4 clone unsuitable for industrial development and regulatory purposes, and limiting the specificity of tumor therapy in determining the success of a treatment, etc., and achieves the effect of convenient use in tumor therapy
Inactive Publication Date: 2008-10-21
ALFASIGMA SPA
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- Application Information
AI Technical Summary
Benefits of technology
ST2146 demonstrates improved homogeneity, affinity, and immunoreactivity compared to BC4, with enhanced tumor targeting and reduced toxicity, achieving superior tumor / non-tumor distribution ratios and therapeutic efficacy in cancer treatment.
Problems solved by technology
The specificity of tumor therapy is often a limiting step in determining the success of a treatment.
In fact, the onset of toxic effects and the reduced tolerability of certain anticancer agents limit their use and the quality of life of patients.
The present applicant found the BC4 clone unsuitable for industrial development and regulatory purposes due to the production of an additional, non functional light chain (most likely of parental myeloma origin) whose level of expression increased under the pressure of scaling up cultivation, thus preventing large scale antibody purification.
Method used
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Effect test
example 1
[0073]In order to generate a new hybridoma cell clone with the specificity of BC4 but lacking the expression of non functional light chain, Balb / c mice were immunized with pTn28 E. coli phage lysate. pTn28 is a λgt11 recombinant clone encoding a fragment of the EGF-like repeat of human tenascin previously shown to contain the BC4 epitope (Balza E. et al., 1993). The schematic representation of human tenascin-C, the related recombinant antigenic fragments and reagents, as well as the strategy used to generate a BC-4 like antibody is given in FIG. 1. pTn28 immunized splenocytes were fused to Sp2 / 0Ag14 non producing myeloma cells by standard method (Cianfriglia M. et al., Methods Enzymol. 121:193210, 1986) and the hybridoma population screened by ELISA on SK-MEL-28 (human melanoma cell line) purified tenascin. Tenascin specific hybridomas were cloned by limiting dilution two times in FCS containing medium and three times in protein free medium (Animal Derived Component Free Medium HyCl...
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Abstract
A novel anti-human tenascin ST2146 monoclonal antibody is described endowed with high affinity with the native antigen and high tumor selectivity. The cST2146 hybridoma is stably producing the antibody in high density culture conditions and is suitable for the industrial development of ST2146-based products. ST2146 exhibits properties exploitable for both therapeutic and diagnostic applications.
Description
[0001]This application is the US national phase of international application PCT / IT03 / 00098 filed 20 Feb. 2003, which designated the US and claims benefit of U.S. Application No. 60 / 359,299 filed 26 Feb. 2002, the entire contents of each of which are incorporated herein by reference.[0002]The present invention relates to monoclonal antibodies anti-human tenascin, methods and materials for obtaining them, the use of said antibodies for the preparation of diagnostic means and medicaments for the diagnosis and treatment, respectively, of tumors expressing tenascin and materials comprising said antibodies suitable for use in medical field.BACKGROUND OF THE INVENTION[0003]The specificity of tumor therapy is often a limiting step in determining the success of a treatment. In fact, the onset of toxic effects and the reduced tolerability of certain anticancer agents limit their use and the quality of life of patients.[0004]The reduction of toxicity is directly linked to the selectivity of t...
Claims
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IPC IPC(8): C07K16/00A61K39/395G01N33/53A61K38/00A61K39/00A61K49/00A61P35/00C07K16/18C07K16/30C07K16/46C12N1/15C12N1/19C12N1/21C12N5/10C12N5/20C12N15/09C12P21/08G01N33/574
CPCC07K16/18C07K16/30G01N33/574A61K2039/505C07K2317/31C07K2317/565G01N2333/78Y10S435/81Y10S435/975A61P35/00C07K16/28C07K16/42
Inventor DE SANTIS, RITAANASTASI, ANNA MARIA
Owner ALFASIGMA SPA